Conduct Disorder (CD) and depression are highly comorbid conditions in childhood and adolescence. This comorbidity is associated with increased risk for several adverse outcomes, including social rejection, substance use, anxiety disorders, and suicide. However, because much of the extant research in this area has been conducted at the symptom level, relatively little is known about the mechanisms of action that are responsible for the observed rates of comorbidity. Moreover, a number of plausible alternatives obtain. Identifying which of these mechanisms is at work is likely to require the application of several strategies that have generally not been employed in the comorbidity literature to date. These include (a) distinguishing between childhood-onset and adolescent-onset CD, (b) expanding the scope of comorbidity research to include biological and physiological measures, (c) generating and testing mechanistic theories of comorbidity, and (d) studying the development of comorbidity and its associated symptoms longitudinally. In the proposed research, each of these issues will be addressed in a study including childhood-onset conduct-disordered, depressed, comorbid (conduct-disordered + depressed), and control preadolescents, ages 8-12. Studies conducted within this age range are critical, as it represents a period of escalating delinquency, depression, and substance use, which often co-occur. Following from theories of emotion regulation (Porges, 1995) and motivation (Gray, 1 982a, 1 982b, 1 987a, 1 987b), patterns of psychophysiological responding will be assessed in participants during conditions of reward, punishment, and social threat. In addition, extensive family history interviews with be conducted with parents, and measures of child delinquency, symptoms of depression, and substance use will be obtained at each of three one-year intervals. Using these data, the following Specific Aims will be pursued: (1) elucidate patterns of autonomic nervous system activity within and across groups through assessment of appropriate psychophysiological markers of behavioral inhibition (electrodermal responding during punishment), behavioral activation (cardiac pre-ejection period during reward), and emotion regulation (respiratory sinus arrhythmia during social threat); (2) assess developmental trajectories in autonomic responding within and across disorders, and relate these trajectories to parental background characteristics and parenting practices; and (3) assess developmental trajectories in child substance use patterns, and examine the potential mediating roles of autonomic responding in relations between parental and child use. Findings obtained should further our understanding of the autonomic substrates of CD, depression, and their comorbidity, and may have differential treatment implications for depressed probands who do and do not present with comorbid CD.